Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study

BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK's largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity

The pre-vaccination regional epidemiological landscape of measles in Italy: contact patterns, effort needed for eradication, and comparison with other regions of Europe

BACKGROUND: Strong regional heterogeneity and generally sub-optimal rates of measles vaccination in Italy have, to date, hampered attainment of WHO targets for measles elimination, and have generated the need for the new Italian National Measles Elimination Plan. Crucial to success of the plan is the identification of intervention priorities based upon a clear picture of the regional epidemiology of measles derived from the use of data to estimate basic parameters. Previous estimates of measles force of infection for Italy have appeared anomalously low. It has been argued elsewhere that this results from Italian selective under-reporting by age of cases and that the true measles force of infection in Italy is probably similar to that of other European countries. A deeper examination of the evidence for this conjecture is undertaken in the present paper. METHODS: Using monthly regional case notifications data from 1949 to the start of vaccination in 1976 and notifications by age from 1971–76, summary equilibrium parameters (force of infection (FOI), basic reproductive ratio (R(0)) and critical vaccination coverage (p(c))) are calculated for each region and for each of 5 plausible contact patterns. An analysis of the spectra of incidence profiles is also carried out. Finally a transmission dynamics model is employed to explore the correspondence between projections using different estimates of force of infection and data on seroprevalence in Italy. RESULTS: FOI estimates are lower than comparable European FOIs and there is substantial regional heterogeneity in basic reproductive ratios; certain patterns of contact matrices are demonstrated to be unfeasible. Most regions show evidence of 3-year epidemic cycles or longer, and compared with England & Wales there appears to be little synchronisation between regions. Modelling results suggest that the lower FOI estimated from corrected aggregate national data matches serological data more closely than that estimated from typical European data. CONCLUSION: Results suggest forces of infection in Italy, though everywhere remaining below the typical European level, are historically higher in the South where currently vaccination coverage is lowest. There appears to be little evidence to support the suggestion that a higher true force of infection is masked by age bias in reporting

Mining social mixing patterns for infectious disease models based on a two-day population survey in Belgium

<p>Abstract</p> <p>Background</p> <p>Until recently, mathematical models of person to person infectious diseases transmission had to make assumptions on transmissions enabled by personal contacts by estimating the so-called WAIFW-matrix. In order to better inform such estimates, a population based contact survey has been carried out in Belgium over the period March-May 2006. In contrast to other European surveys conducted simultaneously, each respondent recorded contacts over two days. Special attention was given to holiday periods, and respondents with large numbers of professional contacts.</p> <p>Methods</p> <p>Participants kept a paper diary with information on their contacts over two different days. A contact was defined as a two-way conversation of at least three words in each others proximity. The contact information included the age of the contact, gender, location, duration, frequency, and whether or not touching was involved.</p> <p>For data analysis, we used association rules and classification trees. Weighted generalized estimating equations were used to analyze contact frequency while accounting for the correlation between contacts reported on the two different days.</p> <p>A contact surface, expressing the average number of contacts between persons of different ages was obtained by a bivariate smoothing approach and the relation to the so-called next-generation matrix was established.</p> <p>Results</p> <p>People mostly mixed with people of similar age, or with their offspring, their parents and their grandparents. By imputing professional contacts, the average number of daily contacts increased from 11.84 to 15.70. The number of reported contacts depended heavily on the household size, class size for children and number of professional contacts for adults. Adults living with children had on average 2 daily contacts more than adults living without children. In the holiday period, the daily contact frequency for children and adolescents decreased with about 19% while a similar observation is made for adults in the weekend. These findings can be used to estimate the impact of school closure.</p> <p>Conclusion</p> <p>We conducted a diary based contact survey in Belgium to gain insights in social interactions relevant to the spread of infectious diseases. The resulting contact patterns are useful to improve estimating crucial parameters for infectious disease transmission models.</p

Impact of Emerging Antiviral Drug Resistance on Influenza Containment and Spread: Influence of Subclinical Infection and Strategic Use of a Stockpile Containing One or Two Drugs

BACKGROUND: Wide-scale use of antiviral agents in the event of an influenza pandemic is likely to promote the emergence of drug resistance, with potentially deleterious effects for outbreak control. We explored factors promoting resistance within a dynamic infection model, and considered ways in which one or two drugs might be distributed to delay the spread of resistant strains or mitigate their impact. METHODS AND FINDINGS: We have previously developed a novel deterministic model of influenza transmission that simulates treatment and targeted contact prophylaxis, using a limited stockpile of antiviral agents. This model was extended to incorporate subclinical infections, and the emergence of resistant virus strains under the selective pressure imposed by various uses of one or two antiviral agents. For a fixed clinical attack rate, R(0) rises with the proportion of subclinical infections thus reducing the number of infections amenable to treatment or prophylaxis. In consequence, outbreak control is more difficult, but emergence of drug resistance is relatively uncommon. Where an epidemic may be constrained by use of a single antiviral agent, strategies that combine treatment and prophylaxis are most effective at controlling transmission, at the cost of facilitating the spread of resistant viruses. If two drugs are available, using one drug for treatment and the other for prophylaxis is more effective at preventing propagation of mutant strains than either random allocation or drug cycling strategies. Our model is relatively straightforward, and of necessity makes a number of simplifying assumptions. Our results are, however, consistent with the wider body of work in this area and are able to place related research in context while extending the analysis of resistance emergence and optimal drug use within the constraints of a finite drug stockpile. CONCLUSIONS: Combined treatment and prophylaxis represents optimal use of antiviral agents to control transmission, at the cost of drug resistance. Where two drugs are available, allocating different drugs to cases and contacts is likely to be most effective at constraining resistance emergence in a pandemic scenario

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Models of epidemics: when contact repetition and clustering should be included

Background The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. Methods We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. Results The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. Conclusion We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.ISSN:1742-468

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let